1区 · 医学
Article
作者: Wang, Shouming ; Beck, Richard ; Burd, Andrew ; Blench, Toby ; Marlin, Frederic ; Ayele, Tenagne ; Buxton, Stuart ; Dagostin, Claudio ; Malic, Maja ; Joshi, Rina ; Barry, John ; Sajad, Mohammed ; Cheung, Chiming ; Shaikh, Shaheda ; Chahwala, Suresh ; Chander, Chaman ; Baumgartner, Christine ; Holthoff, Hans-Peter ; Murray, Elizabeth ; Blackney, Michael ; Giddings, Amanda
On the basis of our understanding on the binding interactions of the benzothiophene template within the FIXa active site by X-ray crystallography and molecular modeling studies, we developed our SAR strategy by targeting the 4-position of the template to access the S1 beta and S2-S4 sites. A number of highly selective and potent factor Xa (FXa) and FIXa inhibitors were identified by simple switch of functional groups with conformational changes toward the S2-S4 sites.